[Intracellular mechanisms of opioidergic regulation of the myocardial function during normoxia and postischemic reperfusion].

Cardioprotective and inotropic effects of selective agonists of delta1- and k1-opioid receptors (OR): DPDPE (0.1 microM/L) and U-50.488 (0.1 microM/L) were studied during 45 min global ischemia and 30 min reperfusion of the rat isolated perfused heart. Activation of both OR types promoted a 2-fold reduction in reperfusion leakage of creatine kinase. Cardioprotective effect of U-50.488 was accompanied by a 2-fold decrease in cAMP levels in myocardium. The selective delta1-agonist DPDPE had no effect on the cAMP content. Cardioprotective effect of DPDPE was not demonstrated after inhibition of Ca2+-ATPase in sarcoplasmic reticulum (SR) by cyclopiazonic acid. Stimulation of myocardial delta1- and K1-OR decreased the heart rate and force of contraction both before ischemia and during reperfusion. In summary, cardioprotective effect of U-50.488 depends on the reduction in myocardial cAMP levels whereas cytoprotective effect of DPDPE is mediated via opioidergic alteration in Ca2+-transport at SR level. Decrease in pump function of heart in response to OR activation does not depend upon alteration in cAMP levels in the myocardium.